Background Sub-clinical synovial-based inflammation has been documented in inter-critical gout; however, there is no validated scoring system to assess this synovial inflammation. We recently completed a prospective MRI trial assessing the response of sub-clinical, synovial inflammation to nine months of urate lowering therapy (ULT) with febuxostat (1). There was a significant reduction in serum urate levels, but the effect on the synovial inflammation was unclear depending on the scoring system used.
Objectives This is a blinded, post-hoc analysis of these same MRI images using a novel quantitative tool. The presented protocol aims at scoring inter-critical synovitis from MRI data in gout patients.
Methods All participants had inter-critical gout and received a 3T MRI with and without gadolinium of their “index joint” (i.e. the joint most often involved with acute attacks of gout) both before and after ULT. This novel tool utilizes proprietary software to analyze contrast enhanced-MRI images. Volumetric biomarkers reflecting the amount of inflammation are computed in order to compare pre and post treatment scans; the degree of inflammation is quantified and termed normalized intensity values (NormI value). The NormI value is a semi-automatic algorithm using a mean intensity value assessed on axial, coronal, and sagittal measurement planes. The workflow performed includes: 1) Normalize image intensities and compute the NormI map by generating a baseline region in air signal intensity; 2) Adjust the NormI histogram to focus on high image intensities; 3) Outline the index joint by drawing regions of interest (ROIs) in every slice; 4) Group 2D ROIs to a 3D volume of interest (VOI). Regions with positive NormI values correlate with regions of inflammation. Four readers assessed the images and each image was assessed once. The primary endpoint was a blinded comparison of the NormI value in the index joint from baseline to month 9.
Results 25 subjects (19 males; mean age of 57.4 and disease duration of 9.7 years) were assessed; the most common index joint was the 1st MTP (n=21). The average serum urate at baseline and month 9 was 9.3mg/dL (±1.3 SD) and 5.36mg/dL (±1.4 SD), respectively (p<0.0001). The mean NormI value at baseline and month 9 was 1818.42 (±1987.15 SD) and 1128.64 (±1620.04 SD) units, respectively (p=0.001). Figure 1 represents a before (left) and after treatment (right) NormI map. Using the Kruskall-Wallis test, the scores of three out of four readers did not differ statistically significant from each other; one reader differed from the others.
Conclusions In this post-hoc analysis of patients with inter-critical gout, significant improvement in sub-clinical, synovial-based inflammation after 9 months of ULT was detected with this novel MRI-based quantitative tool. This technique deserves further study as a potential tool to assess inter-critical gout.
Carter JD, Patelli M, Anderson SR, Prakash N, Rodriquez EJ, Bateman H, Sterrett A, Valeriano J, Ricca LR. An MRI assessment of chronic synovial-based inflammation in gout and its correlation with serum urate levels. Clin Rheumatol. 2015 Feb;34(2):345-51.
Acknowledgements Study support provided by AstraZeneca
Disclosure of Interest J. Carter Grant/research support from: AstraZeneca; Takeda, Speakers bureau: Takeda, M. Orzechowski: None declared, D. Roettger: None declared, J. Vincent: None declared, M. Hinton: None declared, O. Kubassova: None declared, M. Boesen: None declared
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